VELOCITY: Gene therapy to relieVe the burdEn of LMNA pathOgeniC varIanTs in cardiomYopathy
LMNA-related dilated cardiomyopathy (LMNA-DCM) is a rare hereditary heart muscle disease caused by mutations in the LMNA gene. This gene encodes the structural proteins lamin A and lamin C, which support the integrity and function of heart muscle cells. Defects in this gene weaken the heart muscle over time, leading to progressive enlargement, heart failure, and severe arrhythmias. Symptoms often begin early in adulthood, and there is currently no curative treatment—only therapies that alleviate symptoms and slow disease progression.
The VELOCITY project aims to develop the first curative gene therapy for LMNA-DCM caused by haploinsufficiency—a condition in which one copy of the gene is inactive, reducing the production of essential proteins by half. The novel LMNA/C therapy restores the production of both lamin A and lamin C through the cell’s own natural processing mechanisms.
To validate this therapy, the consortium will conduct experiments in patient-derived stem cell heart models (2D and 3D hiPSC systems) and genetically modified animal models that replicate human disease features. In parallel, patient database analyses will identify the most suitable candidates for future clinical trials and help define reliable intermediate markers for disease progression—an essential step for rare disease studies.
The project unites leading academic and industrial partners: the Hubrecht Institute (coordination by Prof. Eva van Rooij), Phlox Therapeutics (gene therapy development), and experts in molecular cardiology from Maastricht University and the Amsterdam UMC. This unique public–private partnership combines world-class research, clinical expertise, and biotechnology innovation to bring the first potential curative gene therapy for LMNA-DCM closer to patients.
